PROJECT SUMMARY/ABSTRACT Background: Children with Tuberous Sclerosis Complex (TSC) are at high risk for neurodevelopmental disorders, with rates of autism spectrum disorder (ASD) approaching 60%. Prospective studies have found that infants with TSC demonstrate delays in social communication skills in the first year of life. However, to date no studies have investigated whether early behavioral intervention can improve social communication skills in infants with TSC. Objectives: The overarching goal of the study is to determine if social communication function can be improved in infants with TSC with a targeted, short-term behavioral intervention called JASPER (Joint Attention, Symbolic Play, Engagement, Regulation), and to enrich traditional outcome measures by combining behavioral measures with electrophysiological (EEG) biomarkers of social communication. These biomarkers can capture subtle changes in brain development that may reflect responses to treatment prior to an overt behavioral change, particularly relevant for children with significantly delayed development, and they can inform the neural mechanisms underlying the behavioral changes found with intervention. Hypothesis: It is expected that, compared to a wait list control group, infants receiving the JASPER intervention will demonstrate greater gains in social communication skills, with changes captured both behaviorally and electrophysiologically. Methodology: A total of 60 infants with TSC ages 12-36 months will be recruited across two sites with an established collaboration in TSC research, UCLA and Boston Children's Hospital, with each infant randomized to treatment or wait list control group. The wait list control design allows all infants to receive intervention while still maintaining a non-treatment comparison group. Treatment will consist of 12 weeks of weekly intervention sessions. Assessments (clinical, behavioral and EEG) will be performed before treatment, after treatment, 3 months after completion, and then 12 months after completion. Controls will undergo assessments at the same time points, and then will start intervention at month 6. Assessments will include behavioral measures of social communication skills, cognition, language and adaptive function, and EEG measure of resting state brain activity, visual and face processing. Impact: Early intervention improves cognitive and behavioral outcomes in ASD, yet no studies have investigated the effects of targeted, early behavioral intervention in infants with TSC. Evidence of efficacy of early intervention will justify its value for all infants with TSC, improving developmental outcomes and attenuating symptoms that lead to the diagnosis of neurodevelopmental disabilities in TSC. Moreover, this study holds relevance for intervention research across neurodevelopmental disorders through its integration of EEG biomarkers with behavioral measures, as such methodology may more readily capture the effects of treatment in pre-verbal and developmentally delayed infants.